A cyclen-based fluoropolymer as a versatile vector for gene and protein delivery. (5th May 2022)

• Record Type: Journal Article
• Authors: Huang, Zheng; Xiao, Ya-Ping; Guo, Yu; Yang, Hui-Zhen; Zhao, Rui-Mo; Zhang, Ji; Yu, Xiao-Qi
• Is Part Of: European polymer journal. Volume 170(2022)
• Publication Date: 2022-05-05
• Subjects: Fluoropolymer -- Gene transfection -- Protein delivery -- Cyclen; Polymers -- Periodicals; Polymerization -- Periodicals; Polymères -- Périodiques; Polymérisation -- Périodiques; Polymerization; Polymers; Periodicals; Electronic journals; 547.705
• DOI: 10.1016/j.eurpolymj.2022.111153
• Languages: English
• ISSNs: 0014-3057

Abstract

Graphical abstract: Highlights: A polymer combining Zn-cyclen and multifluoro-backbone structures was designed. Zn-coordination could largely improve both gene and protein delivery efficiency. Title polymer could give higher gene transfection efficiency than PEI 25 kDa. The polymer mediated effective protein delivery while maintaining the protein activity. Abstract: Gene and protein therapy have shown great potential in the treatment of severe human diseases. It's increasingly necessary for the development of multifunctional vectors that can stabilize the gene / protein and deliver them into cells. Herein, a novel polymer composed of fluorinated linkage and Zn-coordinated macrocyclic polyamine (cyclen) was designed and synthesized via ring-opening polymerization. The Zn-cyclen moiety contributes to the gene transfection efficiency, while the fluorinated backbone might afford the protein delivery ability. Experimental results demonstrated that Zn-coordination could improve the water solubility of the polymer and the stability of the polyplexes formed with DNA. For gene transfection, the target polymer ZnCF4 could give similar to or slightly higher efficiency than the golden standard PEI 25 kDa in various cell lines. Several assays revealed that the improvement of transfection efficiency by the Zn-coordination might come from higher polyplex stability, better cellular uptake, and efficient endosome escape. For protein delivery, the Zn-coordination could also largely enhance the efficiency. β-Galactosidase assay revealed that ZnCF4 could not only effectively transfer protein into cells, but also maintain the protein activity. These results suggest that the title polymer might be a versatile platform for the delivery of various bioactive macromolecules, showing its potential in gene and protein therapy.